Francisella tularensis is the highly infectious intracellular bacterium that causes tularemia and is a potential agent of bioterrorism.

We are interested in understanding how Francisella evades defenses innate so efficiently that even a few bacteria can cause a life-threatening disseminated infection. In particular, we study how the major surface glycolipid of Francisella, lipopolysaccharide (LPS), modulates interactions with host immunity.

We have previously shown that host the LPS-recognition proteins, LPS-binding protein (LBP) and bactericidal/permeability-increasing protein (BPI) fail to bind Francisella LPS. Using a variety of chromatographic methods in concert with metabolic labeling of bacterial lipids, we are characterizing the structural heterogeneity of Francisella LPS, with the goal understanding the structural determinants of its ability to evade recognition by host innate proteins.

We have also recently demonstrated that nonimmune human serum contains IgM that binds to F. tularensis and mediates complement opsonization, which results in efficient ingestion by host phagocytes. The precise structure bound by the IgM appears to be the LPS O-antigen, but we are currently defining the basis of this recognition more specifically. Whether complement activation facilitates infection of host cells in which the bacterium grows or rather promotes host defense remains unclear, but is a focus of current studies.